CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Role of Natural Killer T (NKT) Cells in Myeloma Biology and Therapy.
Role of Natural Killer T (NKT) Cells in Myeloma Biology and Therapy.
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自然杀伤T（NKT）细胞是一种独特的固有淋巴细胞，能够识别由非多态性分子CD1d提呈的脂质抗原。多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，其中恶性浆细胞表达CD1d并对NKT细胞介导的裂解敏感。MM中恶性进展的特征是NKT细胞功能障碍。多项研究尝试利用NKT细胞的抗肿瘤特性在MM中介导肿瘤消退。NKT细胞也是MM中免疫重定向策略（如嵌合抗原受体NKT（CAR-NKT）和双特异性抗体）的有吸引力的靶点。除了常被研究的恒定NKT（iNKT）细胞外，MM患者还常表现出II型NKT细胞及其配体的改变。在戈谢病（GD）患者和小鼠模型中——GD是一种遗传性脂质贮积病，MM风险显著增加——不同的II型NKT细胞表现出T滤泡辅助（NKT-TFH）表型，并为脂质特异性B细胞提供辅助。
在此背景下，慢性免疫激活最终为恶性肿瘤的发生奠定基础，而通过减少潜在的抗原，可在小鼠模型和GD患者中靶向这一过程。因此，NKT细胞与MM发病机制密切相关，是MM免疫治疗的一个有吸引力的靶点。
Natural Killer T (NKT) cells are distinct innate lymphocytes that recognize lipid antigens in the context of nonpolymorphic molecule CD1d. Multiple myeloma (MM) is a hematologic malignancy wherein malignant plasma cells express CD1d and are sensitive to lysis by NKT cells.
Progressive malignancy in MM is characterized by NKT cell dysfunction. Several studies have tried to harness the anti-tumor properties of NKT cells in MM to mediate tumor regression. NKT cells are also attractive targets for approaches at immune redirection in MM with chimeric-antigen receptor NKT (CAR-NKT) and bispecific antibodies.
In addition to the commonly studied invariant-NKT (iNKT) cells, MM patients often also exhibit alterations in type-II NKT cells and their ligands. In patients and mouse models with Gaucher disease (GD), an inherited lipid-storage disorder with markedly increased risk for MM, distinct type-II NKT cells exhibit a T-follicular helper (NKT-TFH) phenotype and provide help to lipid-specific B cells.
Chronic immune activation in this setting eventually sets the stage for malignancy, which can be targeted in both mouse models and GD patients by reducing the underlying antigen. NKT cells are thus integrally linked to MM pathogenesis and an attractive target for MM immunotherapy.
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